5-Oxa-13,14-didehydro-PGE1 compounds

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 657,739, filed Feb. 13, 1976, now issued as U.S. Pat. No. 4,029,681 on June 14, 1977.

The present invention relates to prostaglandin analogs for which the essential material constituting a disclosure therefor is incorporated by reference here from U.S. Pat. No. 4,029,681, issued June 14, 1977. 

I claim:
 1. A prostaglandin analog of the formula: ##STR1## wherein D is ##STR2## wherein Y₁ is --C.tbd.C--; wherein g is 1, 2, or 3;Wherein m is 1 to 5, inclusive; Wherein M₁ is ##STR3## wherein R₅ and R₆ are hydrogen or methyl, with the proviso that one of R₅ and R₆ is methyl only when the other is hydrogen; Wherein L₁ is ##STR4## or a mixture of ##STR5## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is fluoro only when the other is hydrogen; and Wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, two, or three chloro or alkyl of one to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation.
 2. A compound according to claim 1, wherein D is ##STR6##
 3. A compound according to claim 2, wherein M₁ is ##STR7## and g is
 1. 4. A compound according to claim 3, wherein R₃, R₄, R₅, and R₆ are all hydrogen.
 5. A compound according to claim 2, wherein M₁ is ##STR8## and g is
 1. 6. A compound according to claim 2, wherein R₃ and R₄ are both hydrogen.
 7. A compound according to claim 6, wherein R₅ is methyl.
 8. A compound according to claim 6, wherein R₆ is methyl.
 9. 5-Oxa-13,14-didehydro-8β,12α-PGE₁, 15-methyl ether, a compound according to claim
 8. 10. A compound according to claim 6, wherein R₅ and R₆ are both hydrogen.
 11. 5-Oxa-13,14-didehydro-8β,12α-PGE₁, a compound according to claim
 10. 12. A compound according to claim 2, wherein at least one of R₃ and R₄ is methyl.
 13. A compound according to claim 12, wherein R₃ and R₄ are both methyl.
 14. A compound according to claim 13, wherein R₅ is methyl.
 15. 5-Oxa-15,16,16-trimethyl-13,14-didehydro-8β,12α-PGE₁, a compound according to claim
 14. 16. A compound according to claim 13, wherein R₆ is methyl.
 17. 5-Oxa-16,16-dimethyl-13,14-didehydro-8β,12α-PGE₁, 15-methyl ether, a compound according to claim
 16. 18. A compound according to claim 13, wherein R₅ and R₆ are both hydrogen.
 19. 5-Oxa-16,16-dimethyl-13,14-didehydro-8β,12α-PGE₁, a compound according to claim
 18. 20. A compound according to claim 2, wherein at least one of R₃ and R₄ is fluoro.
 21. A compound according to claim 20, wherein R₃ and R₄ are both fluoro.
 22. A compound according to claim 21, wherein R₅ is methyl.
 23. 5-Oxa-15-methyl-16,16-difluoro-13,14-didehydro-8β,12.alpha.-PGE₁, a compound according to claim
 22. 24. A compound according to claim 22, wherein R₆ is methyl.
 25. 5-Oxa-16,16-difluoro-13,14-didehydro-8β,12α-PGE₁, 15-methyl ether, a compound according to claim
 24. 26. A compound according to claim 22, wherein R₅ and R₆ are both hydrogen.
 27. 5-Oxa-16,16-difluoro-13,14-didehydro-8β,12α-PGE₁, a compound according to claim
 26. 28. A compound according to claim 1, wherein D is ##STR9##
 29. A compound according to claim 28, wherein M₁ is ##STR10## and g is
 1. 30. A compound according to claim 29, wherein R₃, R₄, R₅, and R₆ are all hydrogen.
 31. A compound according to claim 28, wherein M₁ is ##STR11## and g is
 1. 32. A compound according to claim 31, wherein R₃ and R₄ are both hydrogen.
 33. A compound according to claim 32, wherein R₅ is methyl.
 34. A compound according to claim 32, wherein R₆ is methyl.
 35. 5-Oxa-13,14-didehydro-PGE₁, 15-methyl ether, a compound according to claim
 34. 36. A compound according to claim 32, wherein R₅ and R₆ are both hydrogen.
 37. 5-Oxa-13,14-didehydro-PGE₁, a compound according to claim
 36. 38. A compound according to claim 31, wherein at least one of R₃ and R₄ is methyl.
 39. A compound according to claim 38, wherein R₃ and R₄ are both methyl.
 40. A compound according to claim 39, wherein R₅ is methyl.
 41. 5-Oxa-15,16,16-trimethyl-13,14-didehydro-PGE₁, a compound according to claim
 40. 42. A compound according to claim 39, wherein R₆ is methyl.
 43. 5-Oxa-16,16-dimethyl-13,14-didehydro-PGE₁, 15-methyl ether, a compound according to claim
 42. 44. A compound according to claim 39, wherein R₅ and R₆ are both hydrogen.
 45. 5-Oxa-16,16-dimethyl-13,14-didehydro-PGE₁, a compound according to claim
 44. 46. A compound according to claim 31, wherein at least one of R₃ and R₄ is fluoro.
 47. A compound according to claim 46, wherein R₃ and R₄ are both fluoro.
 48. A compound according to claim 47, wherein R₅ is methyl.
 49. 5-Oxa-15-methyl-16,16-difluoro-13,14-didehydro-PGE₁, a compound according to claim
 48. 50. A compound according to claim 47, wherein R₆ is methyl.
 51. 5-Oxa-16,16-difluoro-13,14-didehydro-PGE₁, 15-methyl ether, a compound according to claim
 50. 52. A compound according to claim 47, wherein R₅ and R₆ are both hydrogen.
 53. 5-Oxa-16,16-difluoro-13,14-didehydro-PGE₁, a compound according to claim
 52. 